Borger Julius, Zweck Elric, Moos Constanze, Horn Patrick, Voß Fabian, Schultheiss Heinz-Peter, Møller Jacob Eifer, Boeken Udo, Aubin Hug, Lichtenberg Artur, Kelm Malte, Roden Michael, Polzin Amin, Westenfeld Ralf, Szendroedi Julia, Scheiber Daniel
Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
Department of Cardiovascular Surgery, University Heart Centre Freiburg, University Hospital Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
ESC Heart Fail. 2025 Apr;12(2):1246-1255. doi: 10.1002/ehf2.15133. Epub 2024 Oct 30.
Myocardial inflammation and impaired mitochondrial oxidative capacity are hallmarks of heart failure (HF) pathophysiology. The extent of myocardial inflammation in patients suffering from ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and its association with mitochondrial energy metabolism are unknown. We aimed at establishing a relevant role of cardiac inflammation in the impairment of mitochondrial energy production in advanced ischaemic and non-ischaemic HF.
We included 81 patients with stage D HF (ICM, n = 44; DCM, n = 37) undergoing left ventricular assist device implantation (n = 59) or heart transplantation (n = 22) and obtained left ventricular tissue samples during open heart surgery. We quantified mitochondrial oxidative capacity, citrate synthase activity (CSA) and fibrosis and lymphocytic infiltration. We considered infiltration of >14 CD3 cells/mm relevant inflammation.
Patients with ICM or DCM did not differ regarding age (61.5 ± 5.7 vs. 56.5 ± 12.7 years, P = 0.164), sex (86% vs. 84% male, P = 0.725), type 2 diabetes mellitus (34% vs. 18%, P = 0.126) or chronic kidney disease (8% vs. 11%, P = 0.994). ICM exhibited oxidative capacity reduced by 23% compared to DCM (108.6 ± 41.4 vs. 141.9 ± 59.9 pmol/(smg), P = 0.006). Maximum production of reactive oxygen species was not significantly different between ICM and DCM (0.59 ± 0.28 vs. 0.69 ± 0.36 pmol/(sml), P = 0.196). Mitochondrial content, detected by CSA, was lower in ICM (359.6 ± 164.1 vs. 503.0 ± 198.5 nmol/min/mg protein, P = 0.002). Notably, relevant inflammation was more common in ICM (27% vs. 6%, P = 0.024), and the absolute number of infiltrating leucocytes correlated with lower oxidative capacity (r = -0.296, P = 0.019). Fibrosis was more prevalent in ICM (20.9 ± 21.2 vs. 7.2 ± 5.6% of area, P = 0.002), but not associated with oxidative capacity (r = -0.13, P = 0.327).
More than every fourth ICM patient with advanced HF displays myocardial inflammation in the range of inflammatory cardiomyopathy associated with reduced mitochondrial oxidative capacity. Future studies may evaluate inflammation in ICM at earlier stages in standardised fashion to explore the therapeutic potential of immunosuppression to influence trajectories of HF in ICM.
心肌炎症和线粒体氧化能力受损是心力衰竭（HF）病理生理学的标志。缺血性心肌病（ICM）或扩张型心肌病（DCM）患者的心肌炎症程度及其与线粒体能量代谢的关系尚不清楚。我们旨在确定心脏炎症在晚期缺血性和非缺血性HF线粒体能量产生受损中的相关作用。
我们纳入了81例D期HF患者（ICM，n = 44；DCM，n = 37），这些患者接受了左心室辅助装置植入（n = 59）或心脏移植（n = 22），并在心脏直视手术期间获取左心室组织样本。我们对线粒体氧化能力、柠檬酸合酶活性（CSA）、纤维化和淋巴细胞浸润进行了量化。我们将每平方毫米>14个CD3细胞的浸润视为相关炎症。
ICM或DCM患者在年龄（61.5±5.7岁 vs. 56.5±12.7岁，P = 0.164）、性别（男性86% vs. 84%，P = 0.725）、2型糖尿病（34% vs. 18%，P = 0.126）或慢性肾脏病（8% vs. 11%，P = 0.994）方面无差异。与DCM相比，ICM的氧化能力降低了23%（108.6±41.4 vs. 141.9±59.9 pmol/（smg），P = 0.006）。ICM和DCM之间活性氧的最大产生量无显著差异（0.59±0.28 vs. 0.69±0.36 pmol/（sml），P = 0.196）。通过CSA检测的线粒体含量在ICM中较低（359.6±164.1 vs. 503.0±198.5 nmol/min/mg蛋白，P = 0.002）。值得注意的是，相关炎症在ICM中更常见（27% vs. 6%，P = 0.024），浸润白细胞的绝对数量与较低的氧化能力相关（r = -0.296，P = 0.019）。纤维化在ICM中更普遍（20.9±21.2 vs. 7.2±5.6%面积，P = 0.002），但与氧化能力无关（r = -0.13，P = 0.327）。
超过四分之一的晚期HF的ICM患者表现出与线粒体氧化能力降低相关的炎症性心肌病范围内的心肌炎症。未来的研究可以以标准化方式评估ICM早期阶段的炎症，以探索免疫抑制对影响ICM中HF病程的治疗潜力。
